Analysis of phase interactions between heart rate variability, respiration and peripheral microhemodynamics oscillations of upper and lower extremities in human

https://doi.org/10.1016/j.bspc.2021.103091Get rights and content

Highlights

  • Phase interactions between HRV, respiration and peripheral hemodynamics were studied.

  • High significant coherence was obtained for all signal pairs at 0.1 Hz.

  • There was high coherence for blood volume oscillations and HRV/respiration at ~0.3 Hz.

  • There was low coherence for blood flow oscillations with HRV/respiration at ~0.3 Hz.

  • The observed phase interactions were similar for upper and lower extremities.

Abstract

Wavelet phase coherence (WPC) between heart rate variability (HRV), respiration, forearm/foot skin blood flow (SBFforearm and SBFfoot) and finger/toe tissue blood volume (TBVfinger and TBVtoe) oscillations were studied in healthy volunteers at rest. SBF was recorded from the outer surface of the right forearm and the dorsum of the right foot. TBV was registered on the right index finger and the right second toe. The significance of obtained WPC values was tested with surrogate method. The observed phase interactions between all analyzed signals were similar for upper and lower extremities. At heart rate frequency (~1 Hz) significant WPC (sWPC) was high for SBFforearm – SBFfoot and TBVfinger –TBVtoe pairs for the most subjects that are explained by cardiac output as the central mechanism of their generation. High sWPC values for HRV – SBFforearm, HRV – SBFfoot, HRV – TBVfinger, HRV – TBVtoe, SBFforearm – SBFfoot and TBVfinger – TBVtoe pairs were found at the frequency of 0.1 Hz for the most participants. We assumed the existence of similar mechanisms that regulate the peripheral microhemodynamics at this frequency. At respiration frequency (~0.3 Hz) sWPC values were high for HRV – TBVfinger/toe, RES –TBVfinger/toe and TBVfinger – TBVtoe pairs for the most persons. In contrary, at this frequency sWPC was low for HRV –SBF forearm/foot, RES – SBFforearm/foot and SBFforearm – SBFfoot pairs. The differences obtained may be associated with the contribution of sympathetic nerve activity to the control of the vascular tone of vessels under study.

Introduction

Human cardiovascular system is known to exhibit oscillations of different genesis. Some oscillations are related to heart activity and its regulation [1], [2]. The other ones associated with oscillations of macro- and microvessel tone and its regulatory mechanisms [3], [4], [5], [6]. Within the context of network physiology, which focuses on the interactions between different oscillation processes across multiple scales of time and space, studies can be aimed at analyzing how different physiological parameters may play distinct roles in their respective regulatory mechanisms [7], [8], [9], [10]. Coordinated work and interaction of these regulatory systems ensure the normal functioning of cardiovascular system, in general, and peripheral microhemodynamics, in particular. Heart rate regulation as well as peripheral blood flow regulation is due to the influence of different factors (respiration, baroreflex, thermoregulation, circadian rhythms, physical activity, stress etc.) which cause heart rate variability (HRV) and complexity of peripheral blood flow oscillations [1], [2], [11], [12], [13], [14]. The complex interactions that give rise to HRV involve coupled physiological oscillators operating over a wide range of different frequencies [15]. Functioning of the human cardiovascular system can be assessed through the analysis of its associated parameters, such HRV (derived from electrocardiogram), skin blood flow (SBF) and tissue blood volume (TBV). HRV has a pattern of several oscillatory frequency components that correspond to respiration, blood pressure oscillations and seems to be related to control of vascular tone and temperature [2]. Moreover, blood flow and tissue blood volume are regulated by the change of the vessel tone that may be responsible for the oscillation generation [11]. Laser Doppler flowmetry (LDF) and photoplethysmography (PPG) are the noninvasive methods for monitoring peripheral hemodynamics. They are used to give information about blood flow oscillations in peripheral vessels. The evaluation of couplings both between regulatory systems and interactions between processes of skin blood flow regulation in different parts of microvascular bed is performed using wavelet phase coherence (WPC) [15], [16], [17], [18], group WPC [15], [19] or nonlinear modeling and dynamical Bayesian inference [20], [21]. The correct assessment of interaction between mechanisms that regulate functionally different components of cardiovascular system, including heart and peripheral blood flow, is necessary to reveal functional changes in cardiovascular system caused by external influences or pathologies.

Currently, a number of studies are aimed at finding and assessing couplings between systems of blood flow regulation and demonstrate the presence and change of phase relationships between regulatory processes both at rest and under external influences, age-related changes or pathological disorders. The change in WPC between oscillations of temperature and skin blood flow in healthy volunteers in response to cold stress was revealed in neurogenic and myogenic intervals [16], [22]. Early we obtained high median WPC values for contralateral forearm skin blood flow in cardiac, respiratory and myogenic intervals in healthy volunteers at rest [23]. In patients with type 1 diabetes mellitus a weakening of phase interactions between respiratory activity and peripheral pulse was found [24]. The couplings between cardiac rhythm and respiration or vascular myogenic activity decreased significantly in aging [15]. Also, it was found that coupling from vascular myogenic activity was significantly weaker in treated hypertension subjects [15]. In our previous study a significant phase coherence was found between forearm skin blood flow oscillations and finger-pad tissue blood volume ones in the low frequency range (0.0095–0.1 Hz) and at the frequency of heart rate (~1 Hz) [25]. At respiration frequency (~0.3 Hz), differences in phase coherence of peripheral hemodynamic oscillations (blood volume and blood flow) with both HRV and respiration were revealed. High phase synchronization with both HRV and respiration was observed for finger-pad tissue blood volume oscillations, and low phase synchronization was for forearm blood flow oscillations in both cases [25].

The regulation of microhemodynamics was shown to differ in various anatomical areas. Less sensitivity of microvascular bed in legs was demonstrated versus arms [26], [27], [28]. However, a few studies dedicated skin microhemodynamics in the upper and lower extremities in humans are controversial. In particular, skin blood perfusion and amplitudes of peripheral blood oscillations were significantly lower in all frequency intervals at rest in legs than in forearms in healthy volunteers [29]. On the contrary, it was shown higher endothelial, sympathetic and myogenic activity of skin microvessels in lower extremities than in upper ones at rest and a decrease of these parameters on leg versus forearm in response to local heating [30], [31], [32], [33]. The differences of SBF regulation between upper and lower extremities are considered to be due to increased blood pressure in lower extremities associated with the upright posture [34]. Thus, studies of phase interactions between cardiovascular oscillations are fragmentary. We hypothesize that phase interactions are a key factor in functioning of complex systems and therefore it is necessary to investigate the coupling parameters underlying cardiac, respiratory and vascular regulation at both central and peripheral levels. In addition, we assume that mechanisms regulating blood volume of finger tissues may be different from mechanisms regulating blood perfusion of forearm/foot skin. We also suggest that these differences may be distinct for the upper and lower extremities. Thus, the aim of the study was to investigate phase interactions between respiration, HRV and peripheral hemodynamic oscillations (skin blood flow and tissue blood volume) of upper and lower extremities in healthy volunteers at rest.

Section snippets

Participants

Twenty-two healthy normotensive persons (13 males and 9 females; mean age 33 ± 8 years; height 172 ± 4sm; weight 68 ± 11 kg; arterial blood pressure 109 ± 13/74 ± 10 mm Hg; HR 68 ± 11 beats/min) took part in the study. All participants had no pathologies of cardiovascular and respiratory systems, diabetes and other chronic and acute diseases. Participants did not smoke and take any vasoactive substances and any medication. They avoided from caffeine- and alcohol- containing drinks at least 12 h

Results

Phase coherence between SBFforearm –SBFfoot and TBVfinger –TBVtoe pairs is shown in Fig. 3. High phase coupling was revealed for both signal pairs at the frequency of heart rate (~1 Hz). The median of WPC for TBV oscillations was significant for all participants and was close to 1. For SBF oscillations this parameter was also significant for all participants but was lower (Me ~ 0.6) than for TBV oscillations. Similarities of phase interactions were also found for both signal pairs at the

Discussion

We conducted a comprehensive study of HRV, respiration, skin blood flow and tissue blood volume oscillations in healthy volunteers at rest to analyze phase interactions between these physiological processes. The following results were obtained: 1) at the frequency of 0.1 Hz significant phase coherence was high for HRV – SBFforearm, HRV – SBFfoot, HRV – TBVfinger, HRV – TBVtoe, SBFforearm – SBFfoot and TBVfinger – TBVtoe pairs; 2) at the frequency of 0.3 Hz coherence was high for HRV – TBVfinger

Study limitations

There are some limitations of this study. Firstly, the differences of phase interactions TBV/SBF oscillations of both extremities with HRV and respiration may be associated with chosen PPG technology. In the present study we used the transmissive PPG device but in the case of reflective version the results may differed from the obtained ones. Secondly, in present study high sWPC (>0.6) for TBVfinger – TBVtoe and SBFforearm – SBFfoot pairs in the frequency range below 0.1 Hz was found for ~20%

Conclusions

The comprehensive study of phase interactions between HRV, respiration, skin blood flow and tissue blood volume oscillations of upper and lower extremities in healthy volunteers at rest was conducted. At the heart rate frequency (~1 Hz) sWPC was high for SBFforearm – SBFfoot and TBVfinger –TBVtoe pairs for the most subjects. We assume that this result is due to the central mechanism of their generation – cardiac output. High sWPC values for HRV – SBFforearm, HRV – SBFfoot, HRV – TBVfinger, HRV

CRediT authorship contribution statement

Irina V. Tikhonova: Data curation, Formal analysis, Investigation, Writing – review & editing. Andrey A. Grinevich: Data curation, Formal analysis, Investigation, Software, Visualization, Writing – review & editing. Arina V. Tankanag: Conceptualization, Formal analysis, Software, Supervision, Visualization, Writing – original draft, Writing – review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank participants for their time and patience during the study. The study was supported by the Russian Foundation for Basic Research (grant # 18-015-00292).

References (77)

  • T. Schreiber et al.

    Surrogate time series

    Physica D

    (2000)
  • J. Theiler et al.

    Testing for Nonlinearity in Time-Series - the Method of Surrogate Data

    Physica D

    (1992)
  • U. Hoffmann et al.

    The frequency histogram–a new method for the evaluation of laser Doppler flux motion

    Microvasc. Res.

    (1990)
  • J.U. Meyer et al.

    Vasomotion patterns in skeletal muscle arterioles during changes in arterial pressure

    Microvasc. Res.

    (1988)
  • M. Zamir et al.

    Myogenic activity in autoregulation during low frequency oscillations

    Auton. Neurosci

    (2011)
  • M.E. Muck-Weymann et al.

    Respiratory-dependent laser-Doppler flux motion in different skin areas and its meaning to autonomic nervous control of the vessels of the skin

    Microvasc. Res.

    (1996)
  • P.B. Persson

    Modulation of cardiovascular control mechanisms and their interaction

    Physiol. Rev.

    (1996)
  • T.F.o.t.E.S.o.C.t.N.A.S.o.P. Electrophysiology, Heart Rate Variability, Circulation, 93 (1996), pp....
  • D.D. Heistad et al.

    Interaction of thermal and baroreceptor reflexes in man

    J. Appl. Physiol.

    (1973)
  • J.M. Johnson

    Nonthermoregulatory control of human skin blood flow

    J. Appl. Physiol.

    (1986)
  • L.B. Rowell et al.

    Sustained human skin and muscle vasoconstriction with reduced baroreceptor activity

    J. Appl. Physiol.

    (1973)
  • A. Scheffler et al.

    Spontaneous oscillations of laser Doppler skin blood flux in peripheral arterial occlusive disease

    Int. J. Microcirc. Clin. Exp.

    (1992)
  • R. Fossion et al.

    A physicist's view of homeostasis: how time series of continuous monitoring reflect the function of physiological variables in regulatory mechanisms

    Physiol. Meas.

    (2018)
  • R.P. Bartsch et al.

    Network Physiology: How Organ Systems Dynamically Interact

    PLoS ONE

    (2015)
  • P. Ivanov et al.

    Network Physiology: Mapping Interactions Between Networks of Physiologic

    Networks

    (2014)
  • R. Rizzo et al.

    Network Physiology of Cortico-Muscular Interactions

    Front. Physiol.

    (2020)
  • J.A. Bevan et al.

    Pressure and flow-dependent vascular tone

    FASEB J.

    (1991)
  • D.L. Eckberg

    Physiological basis for human autonomic rhythms

    Ann. Med.

    (2000)
  • J.L. Cracowski et al.

    Human Skin Microcirculation

    Compr Physiol

    (2020)
  • V. Ticcinelli et al.

    Coherence and Coupling Functions Reveal Microvascular Impairment in Treated Hypertension

    Front. Physiol.

    (2017)
  • A. Bandrivskyy et al.

    Wavelet phase coherence analysis: Application to skin temperature and blood flow

    Cardiovasc. Eng.

    (2004)
  • Y.A. Abdulhameed et al.

    Race-specific differences in the phase coherence between blood flow and oxygenation: A simultaneous NIRS, white light spectroscopy and LDF study

    J. Biophotonics

    (2020)
  • G. Lancaster et al.

    Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans

    J. Physiol.

    (2020)
  • I.V. Tikhonova A.A. Grinevich I.E. Guseva A.V. Tankanag Effect of orthostasis on the regulation of skin blood flow in...
  • V. Ticcinelli et al.

    Ageing of the couplings between cardiac, respiratory and myogenic activity in humans

  • M. Elstad et al.

    Oscillatory pattern of acral skin blood flow within thermoneutral zone in healthy humans

    Physiol. Meas.

    (2017)
  • A.V. Tankanag et al.

    An Analysis of Phase Relationships between Oscillatory Processes in the Human Cardiovascular System

    Biophysics

    (2020)
  • S.C. Newcomer et al.

    Different vasodilator responses of human arms and legs

    J. Physiol.

    (2004)
  • View full text